Interaction between cytochrome P450 and other drug-metabolizing enzymes: evidence for an association of CYP1A1 with microsomal epoxide hydrolase and UDP-glucuronosyltransferase

Biochem Biophys Res Commun. 2000 Jul 14;273(3):1048-52. doi: 10.1006/bbrc.2000.3076.


Protein-protein interactions between cytochrome P450 (P450) and other drug-metabolizing enzymes were studied by affinity chromatography using CYP1A1-, glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns. Sodium cholate-solubilized microsomes from phenobarbital-treated rat liver were applied to the columns and the material eluted with buffer containing NaCl was analyzed by immunoblotting. Microsomal epoxide hydrolase (mEH) and UDP-glucuronosyltransferases (UGTs), as well as NADPH-P450 reductase, were efficiently trapped by the CYP1A1 column. Glycine and BSA columns exhibited no ability to retain these proteins. Protein disulfide isomerase and calnexin, non-drug-metabolizing enzymes expressed in the endoplasmic reticulum, were unable to associate with the CYP1A1 column. These results suggest that CYP1A1 interacts with mEH and UGT to facilitate a series of multistep drug metabolic conversions.

MeSH terms

  • Animals
  • Blotting, Western
  • Cattle
  • Chromatography, Affinity
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Epoxide Hydrolases / metabolism*
  • Glucuronosyltransferase / metabolism*
  • Male
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley


  • Cytochrome P-450 CYP1A1
  • Glucuronosyltransferase
  • Epoxide Hydrolases